Measuring Patient-Reported Use and Outcomes From Complementary and Integrative Health Therapies: Development of the Complementary and Integrative Health Therapy Patient Experience Survey.

Background: Assessing the use and effectiveness of complementary and integrative health (CIH) therapies via survey can be complicated given CIH therapies are used in various locations and formats, the dosing required to have an effect is unclear, the potential health and well-being outcomes are many, and describing CIH therapies can be challenging. Few surveys assessing CIH therapy use and effectiveness exist, and none sufficiently reflect these complexities. Objective: In a large-scale Veterans Health Administration (VA) quality improvement effort, we developed the "Complementary and Integrative Health Therapy Patient Experience Survey", a longitudinal, electronic patient self-administered survey to comprehensively assess CIH therapy use and outcomes. Methods: We obtained guidance from the literature, subject matter experts, and Veteran patients who used CIH therapies in designing the survey. As a validity check, we completed cognitive testing and interviews with those patients. We conducted the survey (March 2021-April 2023), inviting 15,608 Veterans with chronic musculoskeletal pain with a recent CIH appointment or referral identified in VA electronic medical records (EMR) to participate. As a second validity check, we compared VA EMR data and patient self-reports of CIH therapy utilization a month after survey initiation and again at survey conclusion. Results: The 64-item, electronic survey assesses CIH dosing (amount and timing), delivery format and location, provider location, and payor. It also assesses 7 patient-reported outcomes (pain, global mental health, global physical health, depression, quality of life, stress, and meaning/purpose in life), and 3 potential mediators (perceived health competency, healthcare engagement, and self-efficacy for managing diseases). The survey took 17 minutes on average to complete and had a baseline response rate of 45.3%. We found high degrees of concordance between self-reported and EMR data for all therapies except meditation. Conclusions: Validly assessing patient-reported CIH therapy use and outcomes is complex, but possible.

Postpartum Hospital Discharge: Birthing Parent Perspectives on Supportive Practices and Areas for Improvement.

BACKGROUND: Postpartum hospital care and individualized discharge preparedness should be part of person-focused health services. Yet, there are limited descriptions of birthing parents' experiences to identify clinical practice strengths and opportunities to improve systems of care. OBJECTIVE: To explore birthing parents' perspectives on supportive healthcare practices and areas for improvement around postpartum hospital discharge. METHODS: In this mixed-methods study, participants completed an online questionnaire and a semistructured, telephone interview at 2 to 3 weeks postpartum. Researchers summarized responses to 2 quantitative questions and conducted a thematic content analysis of interview data. RESULTS: Forty birthing parents participated (90% non-White). According to quantitative responses, most birthing parents were prepared to be discharged (82.5%). Responses to the interview generated 6 broad factors related to postpartum hospital discharge preparedness: inpatient postpartum support, physical and emotional health, patient priorities and agency, clear and relevant information, holistic care, and scheduling and continuity of care. Researchers further identified themes around specific healthcare practices participants described to be supportive and opportunities for improvement. CONCLUSION: Birthing parents articulated multiple contributors to their preparation for postpartum hospital discharge. These perspectives offer insights for strengthening systems of perinatal care and inform measures of quality postpartum care.

Remote Delivery of Mindful Movement Within Healthcare Systems: Lessons Learned From the Veterans Health Administration.

Mindful Movement approaches have been a growing part of the Veterans Health Administration (VA). Innovations in tele-health technology had been an important initiative before the public health emergency to meet the needs of rural veterans as well as challenges in getting to a physical location for care. The onset of the COVID-19 pandemic accelerated this transition to tele-delivery of many practices including mindful movement. This paper aims to share lessons learned from virtual delivery of mindful movement as part of clinical and well-being programs in VA. Benefits of virtual care discussed include the convenience and decreased travel burden; accessibility for adaptive movement options; translation to home practice; and shifting the emphasis to interoceptive skills-building supportive of self-efficacy for exploring and identifying safe movement. Important challenges are also identified such as technology related barriers; teachers trained to meet the need of offering adaptations for a heterogenous population and supporting interoceptive skill-building; and supporting both physical and psychological safety. Examples are provided of medical groups incorporating virtual mindful movement within programs for diabetes and pain care to further explore the potential benefit of these practices being integrated within the care itself, rather than as a separate practice. It is hoped that the lessons learned will provide support for Veterans and staff, and the wider health care community, in what they need to participate in virtual care that is high quality, accessible, and meets the needs for greater health and well-being.

Realist synthesis protocol on the effectiveness of a rapid response system in managing mental state deterioration in acute hospital settings.

INTRODUCTION: Patient mental state deterioration impacts patient outcomes, staff and increases costs for healthcare organisations. Mental state is broadly defined to include not only mental health but a broad range of cognitive, emotional and psychological well-being factors. Mental state deterioration is inconsistently identified and managed within acute and tertiary medical settings. This protocol aims to synthesise the evidence to test and refine initial programme theories that outline the functioning of a rapid response system. METHODS AND ANALYSIS: This synthesis will be guided by Pawson's key steps in realist reviews. We will clarify the scope of synthesis through an initial literature search, focusing on understanding the functioning of rapid response system in managing patients presenting with mental state deterioration in acute hospital settings. Initial programme theories will be refined by developing a search strategy to comprehensively search electronic databases for relevant English language peer-reviewed studies. Additionally, we will search the grey literature for sources to supplement theory testing. An abstraction form will be developed to record the characteristics of literature sources. We will use spreadsheets to code and report contextual factors, underlying mechanisms, and outcome configurations. ETHICS AND DISSEMINATION: As this study is a realist synthesis protocol, ethics approval is not required. Synthesis findings will be published in a peer-reviewed journal and presented at scientific conferences.

Impact of Beyond Fistula programming on economic, psychosocial and empowerment outcomes following female genital fistula repair: A retrospective study.

OBJECTIVE: To retrospectively assess changes in economic status, psychosocial status and empowerment among women who participated in Beyond Fistula reintegration programming following fistula repair. METHODS: We conducted a retrospective study among 100 Beyond Fistula program participants capturing sociodemographic characteristics, obstetric and fistula history, program participation, and our primary outcomes: economic status, psychosocial status, and empowerment via quantitative survey at two time points: before program participation and currently. Data were collected from November 2020 to July 2021 from 2013 to 2019 program participants. We compared outcomes across these two time points using paired t tests or McNemar's tests. RESULTS: The proportion of individuals owning property (28.0% vs. 38.0%, P = 0.006), having a current source of income (19.0% vs. 56.0%, P < 0.001), and saving or investing income (11.0% vs. 37.0%, P < 0.001) increased significantly from pre- to post-programming. We also identified statistically significant increases from pre- to post-programming in self-esteem (5.0 [IQR 4.0-5.0] vs. 5.0 [IQR 5.0-5.0], P < 0.001), reintegration (53.0 [IQR 43.0-69.0] vs. 65.0 [IQR 51.0-72.0], P < 0.001) and level of input into household economic decision making (2.0 [SD 1.0] vs. 2.3 [SD 1.0], P = 0.004). CONCLUSION: Beyond Fistula programming likely improved economic status, psychosocial status, and empowerment of participants. Post-surgical interventions incorporating a holistic approach can advance recovery through supporting psychosocial and economic wellbeing and should be offered to women undergoing genital fistula repair.

A qualitative study to understand sociocultural beliefs around perinatal and neonatal health in rural areas of Mohali, Punjab, India.

Introduction: Globally, 600,000 mothers (15-49 years) die every year due to pregnancy and childbirth-related complications. Wide variations are seen in cultural practices and beliefs surrounding this period of a woman's life. The present study explores the cultural beliefs and practices of women and families during pregnancy and the postnatal period in order to understand what behavioral management strategies are required to improve maternal and infant outcomes during pregnancy and the postpartum period. Methods: The study was conducted in a rural area of Punjab, from December 2019 to March 2021. A total of 20 women (up to 3 months postpartum, age >18 years, were interviewed. Results: In general, women described eating varied and fairly healthy diets during pregnancy, especially nutritious warm food, following traditional practices. Other cultural practices included restrictions on movement and mobile phone use and the use of unsafe home remedies to promote infant safety and wellbeing, such as using gripe water, applying black pencil to the baby's eyes, and feeding the baby honey. A few were not inclined to engage with these and other cultural expectations, preferring instead to follow contemporary practices influenced by social media. These practices included being accompanied by a family member during delivery, celebrating the baby's birth regardless of sex, and early bathing post-delivery. Discussion: It can be concluded that while many traditional practices are still followed in India, there are new beliefs and behaviors arising from an intersection between culture and technology. Developing strategies that acknowledge older beliefs and modern approaches is essential to promoting better antenatal and postpartum care.

Bioaccumulation of mercury in Lake Michigan painted turtles (Chrysemys picta).

Mercury (Hg) contamination of aquatic environments can lead to bioaccumulation in organisms, but most previous work has focused on fish and not on semi-aquatic reptiles such as turtles that traverse both terrestrial and aquatic habitats. Here, we analyzed total Hg (THg) concentrations in 30 painted turtles (Chrysemys picta) collected from Lake Michigan (USA) coastal wetlands in 2013 to determine if (1) turtles bioaccumulated THg from the environment, (2) concentrations differed between turtle liver and muscle tissue, and (3) tissue concentrations were related to environmental concentrations (e.g., sediment THg). All individual turtles had detectable THg concentrations in both liver and muscle tissue. On average, THg concentrations were over three times higher in liver tissue compared to muscle tissue. We found a positive linear relationship between muscle THg concentrations and turtle body mass, a proxy for age, suggesting bioaccumulation in this species. Neither liver nor muscle THg concentrations followed the sediment contaminant gradient in the wetlands. Despite this, location was a strong predictor of tissue concentration in a linear model suggesting that other site-specific characteristics may be important. Overall, our results demonstrate that painted turtles accumulate mercury in liver and muscle tissues at different rates, which may be constrained by local conditions. Further research is needed to better understand the relationship between environmental mercury concentrations and body burdens in animals like turtles that traverse habitats. In addition, long-lived turtles could be incorporated into pollution monitoring programs to provide a more holistic picture of food web contamination and ecosystem health.

Protocol to evaluate sequential electronic health record-based strategies to increase genetic testing for breast and ovarian cancer risk across diverse patient populations in gynecology practices.

BACKGROUND: Germline genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) for individuals including, but not limited to, those with a personal history of ovarian cancer, young-onset (< 50 years) breast cancer, and a family history of ovarian cancer or male breast cancer. Genetic testing is underused overall, and rates are consistently lower among Black and Hispanic populations. Behavioral economics-informed implementation strategies, or nudges, directed towards patients and clinicians may increase the use of this evidence-based clinical practice. METHODS: Patients meeting eligibility for germline genetic testing for breast and ovarian cancer will be identified using electronic phenotyping algorithms. A pragmatic cohort study will test three sequential strategies to promote genetic testing, two directed at patients and one directed at clinicians, deployed in the electronic health record (EHR) for patients in OB-GYN clinics across a diverse academic medical center. We will use rapid cycle approaches informed by relevant clinician and patient experiences, health equity, and behavioral economics to optimize and de-risk our strategies and methods before trial initiation. Step 1 will send patients messages through the health system patient portal. For non-responders, step 2 will reach out to patients via text message. For non-responders, Step 3 will contact patients' clinicians using a novel "pend and send" tool in the EHR. The primary implementation outcome is engagement with germline genetic testing for breast and ovarian cancer predisposition, defined as a scheduled genetic counseling appointment. Patient data collected through the EHR (e.g., race/ethnicity, geocoded address) will be examined as moderators of the impact of the strategies. DISCUSSION: This study will be one of the first to sequentially examine the effects of patient- and clinician-directed strategies informed by behavioral economics on engagement with breast and ovarian cancer genetic testing. The pragmatic and sequential design will facilitate a large and diverse patient sample, allow for the assessment of incremental gains from different implementation strategies, and permit the assessment of moderators of strategy effectiveness. The findings may help determine the impact of low-cost, highly transportable implementation strategies that can be integrated into healthcare systems to improve the use of genomic medicine. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05721326. Registered February 10, 2023. https://www. CLINICALTRIALS: gov/study/NCT05721326.

Development and Implementation of a Flexible Yoga Therapy Protocol in the Group Acupuncture Therapy and Modified Yoga (GAPYOGA) Pilot Study.

Chronic pain is the most common reason U.S. adults seek medical care. Acupuncture and yoga show effectiveness, and a recent study assessed the feasibility of these two modalities for chronic pain at federally qualified health centers. Yoga research is rarely individualized, which is important for chronic pain treatments. Six experienced yoga professionals drew on research and clinical experience to co-create a yoga therapy protocol standardized for replication with flexibility for individual care. Yoga therapy was to be combined with a previously developed flexible acupuncture intervention in a feasibility trial. Categories of practices were identified as relevant and appropriate for chronic pain management in a federally qualified health center. Within each category, specific practices were listed for each provider to select as appropriate. These were based on usefulness for chronic pain, safety, ease of teaching/learning, and cultural appropriateness. The final manual included: (1) stabilizing poses, (2) mobilizing poses, (3) breathing practices, (4) relaxation, (5) mental practices, and (6) applied philosophy. Each participant began with an intake to inform practice selection. Ten subsequent sessions were 30 minutes each, with 1-2 participants receiving simultaneous care. First sessions included diaphragmatic breathing and some physical postures. All practices were adapted. Over 10 sessions, at least one practice from each category was included. Participants were given instructions/images for home practice. Individual charting ensured continuity of care and consistency across sessions. In evidence-informed practice, there exists a tension between replicability and individualization. A flexible protocol allows both. Future application in research and clinical settings will help to determine feasibility and effectiveness.

Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer.

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.

Racial and Ethnic Variation in Complementary and Integrative Health Therapy Use Among US Veterans.

Importance: White individuals are the greatest users of complementary and integrative health (CIH) therapies in the general population, but this might partially be due to differences in age, health condition, and location. Identifying the nuances in racial and ethnic differences in care is one important step to addressing them. Objective: To evaluate racial and ethnic differences in Veterans Affairs (VA)-covered CIH therapy use in a more nuanced manner by examining the association of 5 demographic characteristics, health conditions, and medical facility locations with those differences. Design, Setting, and Participants: Retrospective cross-sectional observational study of VA health care system users, using electronic health record and administrative data at all VA medical facilities and community-based clinics. Participants included veterans with nonmissing race and ethnicity data using VA-funded health care between October 2018 and September 2019. Data were analyzed from June 2022 to April 2023. Main Outcome and Measure: Any use of VA-covered acupuncture, chiropractic care, massage therapy, yoga, or meditation/mindfulness. Results: The sample consisted of 5 260 807 veterans with a mean (SD) age of 62.3 (16.4) years and was 91% male (4 788 267 veterans), 67% non-Hispanic White (3 547 140 veterans), 6% Hispanic (328 396 veterans), and 17% Black (903 699 veterans). Chiropractic care was the most used CIH therapy among non-Hispanic White veterans, Hispanic veterans, and veterans of other races and ethnicities, while acupuncture was the most commonly used therapy among Black veterans. When not accounting for the location of the VA medical facilities in which veterans used health care, Black veterans appeared more likely to use yoga and meditation than non-Hispanic White veterans and far less likely to use chiropractic care, while those of Hispanic or other race and ethnicity appeared more likely to use massage than non-Hispanic White veterans. However, those differences mostly disappeared once controlling for medical facility location, with few exceptions-after adjustment Black veterans were less likely than non-Hispanic White veterans to use yoga and more likely to use chiropractic care. Conclusions and Relevance: This large-scale, cross-sectional study found racial and ethnic differences in use of 4 of 5 CIH therapies among VA health care system users when not considering their medical facility location. Given those differences mostly disappeared once medical facilities were accounted for, the results demonstrated the importance of considering facilities and residential locations when examining racial differences in CIH therapy use. Medical facilities could be a proxy for the racial and ethnic composition of their patients, CIH therapy availability, regional patient or clinician attitudes, or therapy availability.

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Effect of Perioperative Palliative Care on Health-Related Quality of Life Among Patients Undergoing Surgery for Cancer: A Randomized Clinical Trial.

Importance: Involvement of palliative care specialists in the care of medical oncology patients has been repeatedly observed to improve patient-reported outcomes, but there is no analogous research in surgical oncology populations. Objective: To determine whether surgeon-palliative care team comanagement, compared with surgeon team alone management, improves patient-reported perioperative outcomes among patients pursuing curative-intent surgery for high morbidity and mortality upper gastrointestinal (GI) cancers. Design, Setting, and Participants: From October 20, 2018, to March 31, 2022, a patient-randomized clinical trial was conducted with patients and clinicians nonblinded but the analysis team blinded to allocation. The trial was conducted in 5 geographically diverse academic medical centers in the US. Individuals pursuing curative-intent surgery for an upper GI cancer who had received no previous specialist palliative care were eligible. Surgeons were encouraged to offer participation to all eligible patients. Intervention: Surgeon-palliative care comanagement patients met with palliative care either in person or via telephone before surgery, 1 week after surgery, and 1, 2, and 3 months after surgery. For patients in the surgeon-alone group, surgeons were encouraged to follow National Comprehensive Cancer Network-recommended triggers for palliative care consultation. Main Outcomes and Measures: The primary outcome of the trial was patient-reported health-related quality of life at 3 months following the operation. Secondary outcomes were patient-reported mental and physical distress. Intention-to-treat analysis was performed. Results: In total, 359 patients (175 [48.7%] men; mean [SD] age, 64.6 [10.7] years) were randomized to surgeon-alone (n = 177) or surgeon-palliative care comanagement (n = 182), with most patients (206 [57.4%]) undergoing pancreatic cancer surgery. No adverse events were associated with the intervention, and 11% of patients in the surgeon-alone and 90% in the surgeon-palliative care comanagement groups received palliative care consultation. There was no significant difference between study arms in outcomes at 3 months following the operation in patient-reported health-related quality of life (mean [SD], 138.54 [28.28] vs 136.90 [28.96]; P = .62), mental health (mean [SD], -0.07 [0.87] vs -0.07 [0.84]; P = .98), or overall number of deaths (6 [3.7%] vs 7 [4.1%]; P > .99). Conclusions and Relevance: To date, this is the first multisite randomized clinical trial to evaluate perioperative palliative care and the earliest integration of palliative care into cancer care. Unlike in medical oncology practice, the data from this trial do not suggest palliative care-associated improvements in patient-reported outcomes among patients pursuing curative-intent surgeries for upper GI cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03611309.

Urban landscapes and legacy industry provide hotspots for riverine greenhouse gases: A source-to-sea study of the River Clyde.

There is growing global concern that greenhouse gas (GHG) emissions from water bodies are increasing because of interactions between nutrient levels and climate warming. This paper investigates key land-cover, seasonal and hydrological controls of GHGs by comparison of the semi-natural, agricultural and urban environments in a detailed source-to-sea study of the River Clyde, Scotland. Riverine GHG concentrations were consistently oversaturated with respect to the atmosphere. High riverine concentrations of methane (CH4) were primarily associated with point source inflows from urban wastewater treatment, abandoned coal mines and lakes, with CH4-C concentrations between 0.1 - 44 µg l-1. Concentrations of carbon dioxide (CO2) and nitrous oxide (N2O) were mainly driven by nitrogen concentrations, dominated by diffuse agricultural inputs in the upper catchment and supplemented by point source inputs from urban wastewater in the lower urban catchment, with CO2-C concentrations between 0.1 - 2.6 mg l-1 and N2O-N concentrations between 0.3 - 3.4 µg l-1. A significant and disproportionate increase in all GHGs occurred in the lower urban riverine environment in the summer, compared to the semi-natural environment, where GHG concentrations were higher in winter. This increase and change in GHG seasonal patterns points to anthropogenic impacts on microbial communities. The loss of total dissolved carbon, to the estuary is approximately 48.4 ± 3.6 Gg C yr-1, with the annual inorganic carbon export approximately double that of organic carbon and four times that of CO2, with CH4 accounting for 0.03%, with the anthropogenic impact of disused coal mines accelerating DIC loss. The annual loss of total dissolved nitrogen to the estuary is approximately 4.03 ± 0.38 Gg N yr-1 of which N2O represents 0.06%. This study improves our understanding of riverine GHG generation and dynamics which can contribute to our knowledge of their release to the atmosphere. It identifies where action could support reductions in aquatic GHG generation and emission.

Peripheral nerve stimulation: A neuromodulation-based approach.

Recent technological improvements have positioned us at the threshold of innovative discoveries that will assist in new perspectives and avenues of research. Increased attention has been directed towards peripheral nerve stimulation, particularly of the vagus, trigeminal, or greater occipital nerve, due to their unique pathway that engages neural circuits within networks involved in higher cognitive processes. Here, we question whether the effects of transcutaneous electrical stimulation are mediated by synergistic interactions of multiple neuromodulatory networks, considering this pathway is shared by more than one neuromodulatory system. By spotlighting this attractive transcutaneous pathway, this opinion piece aims to acknowledge the contributions of four vital neuromodulators and prompt researchers to consider them in future investigations or explanations.

Supplemental B-Vitamins and Risk of Upper Gastrointestinal Cancers in the Women's Health Initiative.

B-vitamins contribute to DNA synthesis, maintenance, and regulation. Few studies have examined associations of supplemental sources of B-vitamins with the incidence of upper gastrointestinal (GI) cancers [including gastric (GCA) and esophageal (ECA) cancers]; the only prior study to comprehensively examine such intakes reported potential elevated risks of ECA. We examined 159,401 postmenopausal women, ages 50-79 years at baseline, including 302 incident GCA and 183 incident ECA cases, over 19 years of follow-up within the Women's Health Initiative observational study and clinic trials. Adjusted Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of supplemental B-vitamins [riboflavin (B2), pyridoxine (B6), folic acid (B9), or cobalamin (B12)] with GCA and ECA risk, respectively. Although HRs were generally below 1.0, we observed no statistically significant associations between supplemental intakes of any of the evaluated B-vitamins with the risk of GCA or ECA. As the first prospective study to comprehensively assess these associations, our findings do not corroborate prior research indicating potential harm from supplemental B-vitamin intake for upper GI cancer risk. This study adds evidence that supplemental intakes of B-vitamins may be used by postmenopausal women without regard to their relationship with upper GI cancer risk.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

We Built it, But Did They Come: Veterans' Use of VA Healthcare System-Provided Complementary and Integrative Health Approaches.

BACKGROUND: Interest in complementary and integrative health (CIH) approaches, such as meditation, yoga, and acupuncture, continues to grow. The evidence of effectiveness for some CIH approaches has increased in the last decade, especially for pain, with many being recommended in varying degrees in national guidelines. To offer nonpharmacological health management options and meet patient demand, the nation's largest integrated healthcare system, the Veterans Health Administration (VA), greatly expanded their provision of CIH approaches recently. OBJECTIVE: This paper addressed the questions of how many VA patients might use CIH approaches and chiropractic care if they were available at modest to no fee, and would patients with some health conditions or characteristics be more likely than others to use these therapies. DESIGN: Using electronic medical records, we conducted a national, three-year, retrospective analysis of VA patients' use of eleven VA-covered therapies: chiropractic care, acupuncture, Battlefield Acupuncture, biofeedback, clinical hypnosis, guided imagery, massage therapy, meditation, Tai Chi/Qigong, and yoga. PARTICIPANTS: We created a national cohort of veterans using VA healthcare from October 2016-September 2019. KEY RESULTS: Veterans' use of these approaches increased 70% in three years. By 2019, use was 5.7% among all VA patients, but highest among patients with chronic musculoskeletal pain (13.9%), post-traumatic stress disorder (PTSD; 10.6%), depression (10.4%), anxiety (10.2%), or obesity (7.8%). The approach used varied by age and race/ethnicity, with women being uniformly more likely than men to use each approach. Patients having chronic musculoskeletal pain, obesity, anxiety, depression, or PTSD were more likely than others to use each of the approaches. CONCLUSIONS: Veterans' use of some approaches rapidly grew recently and was robust, especially among patients most in need. This information might help shape federal/state health policy on the provision of evidence-based CIH approaches and guide other healthcare institutions considering providing them.

Adapalene/benzoyl peroxide gel 0.3%/2.5% for acne vulgaris

Acne vulgaris is typically treated with a combination of a topical retinoid plus an antimicrobial agent, as recommended by national and international evidence-based guidelines around the globe. Adapalene, a synthetic topical retinoid, is available in two concentrations (0.1% and 0.3%) and in once-daily fixed-dose combinations with benzoyl peroxide (BPO) 2.5%. Adapalene 0.3%/BPO 2.5% is approved for use for moderate-to-severe acne with proven efficacy, good safety and tolerability across a spectrum of patient variables (different ages, genders, and skin types) and disease severity. While some patients experience issues with transient tolerability during retinoid and BPO therapy, it is our clinical experience that good patient education to set expectations and provide strategies to minimize irritation can overcome the majority of issues. This article reviews the data supporting the use of adapalene 0.3%/2.5% in practice, including the complementary mechanism of action of adapalene and BPO, clinical data from a range of settings, and key aspects of patient education.

Anti-inflammatory and wound healing potential of medicinal maggot excretions/secretions at the ocular surface.

PURPOSE: In the skin, Lucilia sericata maggot excretions/secretions (ES) accelerate wound healing and limit inflammation. This study aimed to determine whether ES have similar beneficial effects at the ocular surface. METHODS: Human corneal epithelial cells (HCEC) were cultured with ES and cell viability was determined by the MTT assay. Additionally, mRNA expression of growth factors, antimicrobial peptides (AMPs) and cytokines was assessed by qPCR. ES ability to modulate TLR-induced IL-6 and IL-8 expression was determined by qPCR and ELISA. ES potential to promote corneal healing was evaluated in vitro by a migration assay in HCEC, and in vivo using a mouse model. RESULTS: ES did not impair HCEC viability up to 25 µg/ml. Among the factors evaluated, only hBD-2 was upregulated (2.5-fold) by 1.5 µg/ml ES after 6 hrs (P = 0.04). In HCEC, ES reduced Poly I:C-induced IL-6 and IL-8 mRNA (P ≤ 0.001) and protein (P ≤ 0.0001) expression. A similar effect was observed with Flagellin (TLR5 agonist) but it was less robust for FSL-1 (TLR2/6 agonist) and Pam3CSK4 (TLR1/2 agonist). The greatest in vitro migration effect was observed with 6.2 µg/ml ES after 44 hrs where gap area compared to vehicle was 53.3 ± 3.7% vs. 72.6 ± 5.4% (P = 0.001). In the mouse model, the maximum healing effect was present with 1.5 µg/ml ES after 12 hrs with a wound area of 19.0 ± 2.7% vs. 60.1 ± 21.6% (P = 0.003) or 77% reduction of the wound area compared to the negative control. CONCLUSIONS: ES significantly reduce in vitro TLR-induced production of inflammatory cytokines and promote corneal wound healing.